Most solid cancers contain regions of necrotic (dead) tissue. The extent of necrosis is associated with poor survival, most likely because it reflects aggressive tumour outgrowth and inflammation. The harmless anaerobic bacteria Clostridium sporogenes, upon injection as spores, will germinate and thrive in these necrotic regions, providing cancer-specific colonisation. Through an international collaboration, we have ""armed"" C.sporogenes with a chemotherapy-activating gene that enables the bacteria to be imaged by positron emission tomography. We will characterise the interaction of armed clostridium plus 'masked' chemotherapies developed in our laboratories. We will validate the relationship between tumour necrosis and anti-tumour efficacy. We will also design next-generation 'masked' agents that release inhibitors of DNA repair and investigate their ability to enhance radiation therapy in combination with armed C.sporogenes. This will, for the first time, exploit necrosis in solid cancers, turning this pathological feature associated with treatment failure into a target for precision therapy.